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Department of Defense Comments on the 

NCEA Proposed Draft SAB Peer Review Charge Questions for Dioxin 

Comments submitted by: Robert Boyd Organization: Department of Defense Date Submitted: 13 April 201*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

No. Section 

Page & 

Paragraph or 

Global 

Comment Suggested Action, R

 and References (if ne

1 Global NCEA’s response document discusses modeling 

both animal data and epidemiological data, even though only the epidemiological data are used for quantitative analyses of toxicity values. As the current charge questions take 6 pages, and will take a considerable amount of time by the review panel, we suggest that the questions involving analyses that are not used directly to develop either cancerpotency factors or reference values be eliminated. 

If EPA believes that the animaimportant for an understandinhealth assessment it would be those charge questions reflecsignificance, otherwise we recEPA consider eliminating the to animal data to better focus panel 

2 Section 3; 

1.c. 

With regard to EPA’s modification of the published PBPK model, the question is not clear as to whetherEPA wants comments on the changes made or whether it is appropriate to modify a published, peer-reviewed model without having the modifications peer reviewed. This question is especially relevant as (1) EPA states that their modifications made little difference in the quantitative results (although they do not present the results of the unmodified model) and (2) the model was developed by EPA laboratory scientists and modelers, i.e., this part of EPA is substituting 

their judgment for that of EPA scientists who developed the data and the model. 

As both questions are relevanmodifying the question to readthe modifications implementepublished Emond et al. modefor the analysis and whether smodifications should be exterreviewed prior to their use in a analysis such as this.” 

3 Section 5. 1 As presented, the SAB panel members are likely to 

infer that only one descriptor may be used per chemical. EPA’s 2005 cancer guidelines, however, clearly state (and give examples) that several descriptors may be applied to one chemical. In this case, we suggest that the reviewers be given the option (as one of the examples in EPA’s cancer guidelines) of different descriptors for different intensities of exposure. 

Recommend adding the followafter the last sentence: “EPAguidelines also allow different different exposure levels. Do weight of the evidence suggeacute exposures should be “kcarcinogen” and low, chronic be “likely to be carcinogenic to 
Page 2 of 2 

Department of Defense Comments on the 

NCEA Proposed Draft SAB Peer Review Charge Questions for Dioxin 

Comments submitted by: Robert Boyd Organization: Department of Defense Date Submitted: 13 April 201*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

No. Section 

Page & 

Paragraph or 

Global 

Comment Suggested Action, R

 and References (if ne

4 Section 5.7.b. EPA did not develop one OSF, but presents several 

risk-specific slope factors. As this is a procedure that has not been done before, it is important to ask the reviewers if they are relevant for the use and consistent with current guidance and policy. Moreover, as other questions ask whether this procedure follows EPA’s cancer guidelines, we suggest that this issue be addressed, as this procedure is not consistent with the guidelines. 

Add the following to the end o2005 Cancer Guidelines” statresponse curve is nonlinear a if it is nonlinear with no threshextrapolation below the point should use the reference dose Does this derivation of dose-dfollow the cancer guidelines? of these multiple, risk-specific 

5 Section 5.10 The NAS panel recommended a threshold doseresponse model to characterize dioxin’s 

carcinogenicity. The questions listed in #10 do notdirectly address this issue. 

Recommend adding a questioasks whether EPA gave approconsideration to nonlinear appNAS recommendation. 

6 Section 5. 10 NCEA’s response document models nonlinear 

extrapolations for the animal models but uses epidemiological data to derive its OSFs. EPA’s cancer guidelines indicate that the same point of departure should be used for both the linear and nonlinear extrapolations to low doses. Therefore, the correct comparison should be for those two, andthis should be reflected in the charge questions. 

Add the clause in bold to the t“Are there other nonlinear appincluding the one specified Cancer Guidelines, that couldeveloped based on existing assessment of TCDD carcinoAlso add the following at the eCancer Guidelines specify thasufficient data to indicate that dose-response curve is nonlinapproach should be used from departure. As NCEA has detedeparture for its OSFs, should these be used for an RfD appestimating low-dose cancer ri